Appendix I: publicationHalpin et al. By-products usage. Petfood Industry 1999; May-Jun: 37-40.Download
Appendix II: studies
Diseases demonstrated in the following studies to be more likely following long-term maintenance of cats and dogs on some commercial meat-based diets include kidney, liver, heart, thyroid, neurologic, neuromuscular, skin, and infectious diseases, and bleeding disorders. These studies also illustrate the hazardous ingredients sometimes found within meat-based pet food. I don't condone any invasive animal studies conducted.Bingham AK, Huebner HJ, Phillips TD, Bauer JE. Identification and reduction of urinary aflatoxin metabolites in dogs. Food Chem Toxicol 2004; 42(11): 1851-8.
Hydrated sodium calcium aluminosilicate (HSCAS) is a phyllosilicate clay commonly used as an anticaking agent in animal feeds. HSCAS tightly and selectively adsorbs aflatoxin. In 1998, 55 dogs died in Texas after eating dog food containing aflatoxin (150-300 ppb). The corn in the diets was contaminated with aflatoxin. Six dogs were given a low-level, sub-clinical dose of aflatoxin B(1). On average, 71.5% of aflatoxin M(1) cleared within 6 h after dosing, increasing to 90.4% after 12 h. Aflatoxin M(1) was no longer detectable in urine after 48 h. Aflatoxin P(1) was not found in urine compared to large amounts of M(1) and trace amounts of Q(1). In a crossover study, six dogs randomly fed a commercial dog food (no-clay control) or coated with HSCAS (0.5% by weight) were subsequently administered a sub-clinical dose of aflatoxin B(1). Diets were switched and the process repeated. The HSCAS-coated diet significantly reduced urinary aflatoxin M(1) by 48.4%+/-16.6 SD versus the control diet. In conclusion, HSCAS protects dogs fed diets with even minimal aflatoxin contamination. Despite regular and careful ingredient screening for aflatoxin, low concentrations may reach the final product undetected. Therefore, HSCAS may provide the pet food industry further assurance of canine diet safety. Boyer CI Jr, Andrews EJ, deLahunta A, Bache CA, Gutenman WH, Lisk DJ. Accumulation of mercury and selenium in tissues of kittens fed commercial cat food. Cornell Vet 1978; 68(3): 365-74.
Six kittens, three males and three females, were fed exclusively for one hundred days a commercially canned red meat tuna found to contain elevated concentrations of Mercury (Hg) and Selenium (Se). A similarly sized control group was fed for the same period a dry commercial cat food comparatively low in the concentration of these elements. At the end of the feeding trial, concentrations of Hg Se were markedly higher in blood, bone, brain, kidney, liver, muscle and spleen of the kittens fed the tuna diet as compared to the corresponding controls. No behavioral abnormalities or pathological lesions were detected in any of the kittens. Coleman WE, Tardiff RG. Contaminant levels in animal feeds used for toxicity studies. Arch Environ Contam Toxicol 1979; 8(6): 693-702.
Samples of commercial feeds for laboratory rats, guinea pigs, cats, monkeys, rabbits, and hamsters were collected and analyzed qualitatively and quantitatively for selected antibiotics, trace metals, pesticides (organophosphates and chlorinated hydrocarbons), natural agents, and polychlorinated biphenyls (PCBs). The results indicated that antibiotics, parathion, diazinon, aldrin, and the aflatoxins were not detected, whereas, metals, chlorinated hydrocarbon pesticides (except aldrin), and PCBs were continually present. Malathion and estrogen were found occasionally. DiBartola SP, Buffington CA, Chew DJ, McLoughlin MA, Sparks RA. Development of chronic renal disease in cats fed a commercial diet. J Am Vet Med Assoc 1993; 202(5): 744-51.
Chronic renal failure was observed in 10 young adult client-owned cats that had been fed 1 commercial cat food exclusively since weaning. The diet contained 40% protein and 0.32% potassium on a dry matter basis, and phosphoric acid was added during production. We attempted to determine whether exclusive feeding of this diet would induce clinical and laboratory evidence of renal dysfunction in clinically normal adult cats. Over a 2-year study, 3 of 9 of these cats developed clinical and laboratory evidence of renal dysfunction and renal lesions. Two additional cats developed renal lesions, but had normal laboratory values. The renal lesions consisted of lymphoplasmacytic interstitial nephritis and interstitial fibrosis. We concluded that chronic renal disease may develop in clinically normal adult cats fed diets high in protein and acid content, but marginally replete in potassium. Dobson RLM, Motlagh S, Quijano M, Cambron RT, Baker TR, Pullen AM, Regg BT, Bigalow-Kern AS, Vennard T, Fix A, Reimschuessel R, Overmann G, Shan Y and Daston GP. Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs. Toxicological Sciences 2008; 106(1): 251-62.Download
This paper describes research relating to the major recall of pet food that occurred in Spring 2007 in North America. Clinical observations of acute renal failure in cats and dogs were associated with consumption of wet pet food produced by a contract manufacturer producing for a large number of companies. The affected lots of food had been formulated with wheat gluten originating from China. Pet food and gluten were analyzed for contaminants using several configurations of high performance liquid chromatography (HPLC) and mass spectrometry (MS), which revealed a number of simple triazine compounds, principally melamine and cyanuric acid, with lower concentrations of ammeline, ammelide, ureidomelamine, and N-methylmelamine. Melamine and cyanuric acid, have been tested and do not produce acute renal toxicity. Some of the triazines have poor solubility, as does the compound melamine cyanurate. Pathological evaluation of cats and dogs that had died from the acute renal failure indicated the presence of crystals in kidney tubules. We hypothesized that these crystals were composed of the poorly soluble triazines, a melamine-cyanuric acid complex, or a combination. Sprague dawley rats were given up to 100 mg/kg ammeline or ammelide alone, a mixture of melamine and cyanuric acid (400/ 400 mg/kg/day), or a mixture of all four compounds (400 mg/kg/ day melamine, 40 mg/kg/day of the others). Neither ammeline nor ammelide alone produced any renal effects, but the mixtures produced significant renal damage and crystals in nephrons. HPLC-MS/MS confirmed the presence of melamine and cyanuric acid in the kidney. Infrared microspectroscopy on individual crystals from rat or cat (donated material from a veterinary clinic) kidneys confirmed that they were melamine-cyanuric acid cocrystals. Crystals from contaminated gluten produced comparable spectra. These results establish the causal link between the contaminated gluten and the adverse effects and provide a mechanistic explanation for how two apparently innocuous compounds could have adverse effects in combination, that is, by forming an insoluble precipitate in renal tubules leading to progressive tubular blockage and degeneration. Dow SW, Fettman MJ, Curtis CR, LeCouteur RA. Hypokalemia in cats: 186 cases (1984-1987). J Am Vet Med Assoc 1989; 194(11): 1604-8.
Retrospective review of serum biochemical data obtained from 501 cats over a 3-year period (1984-1987) indicated that 186 (37%) had hypokalemia (serum potassium concentration less than 4.1 mEq/L). After adjusting for disease diagnosis, cats fed either of 2 commercial diets were 4 times more likely to be hypokalemic than cats fed other diets. Odds ratios (OR; measure of association), adjusted for diet type, were calculated to determine the odds of hypokalemia for a given disease, compared with odds of normokalemia for the same disease. Chronic renal failure (OR = 14.4), hepatic disease (OR = 5.7), systemic infectious diseases (viral or bacterial; OR = 2.7), and neuromuscular or CNS disease (OR = 2.4) were all significantly associated (P less than 0.05) with the occurrence of hypokalemia. Significant differences in age or sex between hypokalemic and normokalemic cats were not found. Within the group of 186 hypokalemic cats, hypercholesterolemia (89 cats; 48%), hyperglycemia (88 cats; 47%), high serum urea nitrogen concentration (86 cats; 46%), hyperchloridemia (80 cats; 43%), and high serum creatinine concentration (73 cats; 39%) were the most common biochemical abnormalities. When disease diagnosis was compared among cats with severe hypokalemia (serum potassium concentration less than 3.0 mEq/L) and those with moderate hypokalemia, cats with severe hypokalemia were 3.5 times more likely to have chronic renal failure than cats with less severe hypokalemia.(ABSTRACT TRUNCATED AT 250 WORDS) Freytag TL, Liu SM, Rogers QR, Morris JG. Teratogenic effects of chronic ingestion of high levels of vitamin A in cats. J Anim Physiol Anim Nutr (Berl) 2003; 87(1-2): 42-51.
High concentrations of retinoids occur in some commercial cat food formulations as a result of the use of animal liver as an ingredient. Our objective was to study the teratogenic potential of dietary vitamin A in cats. We investigated the incidence of birth defects in kittens of queens given diets with retinyl acetate concentrations of 6000, 306000, or 606000 retinol equivalents (RE)/kg diet (control, 306K, or 606K groups, respectively) for approximately 3 years [1 RE=1 micro g retinol=3.3 International Units (IU)]. Each group comprised 12-15 age-matched, nulliparous domestic short-haired queens that were exposed to toms. There were a total of 396 kittens born in 97 litters. Pregnancy rate, number of kittens per gestation and gestations per year were not significantly different among treatment groups. A total of 2, 5 and 11 malformed kittens occurred in the control, 306K and 606K groups, respectively. Malformations included cleft palate, cranioschisis, foreshortened mandible, stenotic colon, enlarged heart and agenesis of the spinal cord and small intestine, which are typical foetal defects consistent with ingestion of excess retinoids in other species. This study demonstrated that a concentration of 306000 RE/kg diet has a potential for causing birth defects in the kittens. Houpt KA, Essick LA, Shaw EB, Alo DK, Gilmartin JE, Gutenmann WH, Littman CB, Lisk DJ. A tuna fish diet influences cat behavior. J Toxicol Environ Health 1988; 24(2): 161-72.
When observed in their home cages, cats fed commercial tuna fish cat food were less active, vocalized less, and spent more time on the floor and more time eating than cats fed commercial beef cat food. There were no differences in response to human handling between the two groups. There were no differences in learning ability on a two-choice point maze or in reversal learning in the same maze between beef- and tuna-fed cats. The behavior of the groups differed in a 15-min open field test only in the number of toys contacted. Cats fed the tuna had elevated tissue levels of mercury and selenium. Kass PH, Peterson ME, Levy J, James K, Becker DV, Cowgill LD. Evaluation of environmental, nutritional, and host factors in cats with hyperthyroidism. J Vet Intern Med 1999 13(4): 323-9.
The pathologic changes associated with hyperthyroidism (adenomatous hyperplasia, adenoma of the thyroid gland) have been well characterized in cats, but the pathogenesis of these changes remains unclear. In this research, we undertook a case-control study to search for potential risk factors for this disease. Owners of 379 hyperthyroid and 351 control cats were questioned about their cats' exposure to potential risk factors including breed, demographic factors, medical history, indoor environment, chemicals applied to the cat and environment, and diet. The association between these hypothesized risk factors and outcome of disease was evaluated by conditional logistic regression. Two genetically related cat breeds (ie, Siamese and Himalayan) were found to have diminished risk of developing hyperthyroidism. Cats that used litter had higher risk of developing hyperthyroidism than those that did not. Use of topical ectoparasite preparations was associated with increased risk of developing hyperthyroidism. Compared with cats that did not eat canned food, those that ate commercially prepared canned food had an approximate 2-fold increase in risk of disease. When these 4 variables (breed, use of cat litter, consumption of canned cat food, and use of topical ectoparasite preparations) from the univariate analysis were selected for further study as candidate risk factors and analyzed by multivariate conditional logistic regression, a persistent protective effect of breed (ie, Siamese or Himalayan) was found. In addition, results suggested a 2- to 3-fold increase in risk of developing hyperthyroidism among cats eating a diet composed mostly of canned cat food and a 3-fold increase in risk among those using cat litter. In contrast, the use of commercial flea products did not retain a strong association. The results of this study indicate that further research into dietary and other potentially important environmental factors (eg, cat litter) is warranted. Pion PD, Kittleson MD, Rogers QR, Morris JG. Science. Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science 1987; 237(4816): 764-8.
Thousands of pet cats die each year with dilated cardiomyopathy, the cause of which is unknown. Although taurine is present in millimolar concentrations in the myocardium of all mammals, taurine depletion has not previously been associated with a decrease in myocardial function in any species. In this study, low plasma taurine concentrations associated with echocardiographic evidence of myocardial failure were observed in 21 cats fed commercial cat foods and in 2 of 11 cats fed a purified diet containing marginally low concentrations of taurine for 4 years. Oral supplementation of taurine resulted in increased plasma taurine concentrations and was associated with normalization of left ventricular function in both groups of cats. Since myocardial concentrations of taurine are directly related to plasma concentrations and low plasma concentrations were found to be associated with myocardial failure in cats, a direct link between decreased taurine concentration in the myocardium and decreased myocardial mechanical function is proposed. Sousa CA, Stannard AA, Ihrke PJ, Reinke SI, Schmeitzel LP. Dermatosis associated with feeding generic dog food: 13 cases (1981-1982). J Am Vet Med Assoc 1988; 192(5): 676-80.
The records of 13 dogs with a crusting dermatosis of the mucocutaneous junctions, pressure points, and trunk were evaluated. All of the dogs had been fed corn- and wheat-based commercial dry dog foods that failed to meet the National Research Council's recommendations for balanced nutrition. The dermatosis in all 13 dogs resolved completely after the diet was changed to one that met the National Research Council's recommendations. The disease was similar to that which has previously been called canine dry pyoderma, but is now known to be a zinc-responsive dermatosis. Strieker MJ, Morris JG, Feldman BF, Rogers QR. Vitamin K deficiency in cats fed commercial fish-based diets. J Small Anim Pract 1996; 37(7): 322-6.
Clinical signs of vitamin K deficiency have been observed in cats offered two commercial canned diets high in salmon or tuna. Some of the queens and kittens offered these diets had died while survivors had increased coagulation times. Necropsies revealed hepatic and, or, gastrointestinal haemorrhages. Coagulation times of survivors returned to normal after vitamin K therapy. The purpose of this study was to induce a vitamin K deficiency in kittens and determine the dietary requirement. Kittens were offered vitamin K-deficient purified diets containing antibiotics and, or, substances inherent in canned fish diets that may have contributed to the deficiency. Clinical signs of vitamin K deficiency were not observed, even though one purified diet contained only 4 micrograms K1/kg diet compared with 60 micrograms in the commercial tuna diet. Therefore, a minimum vitamin K requirement could not be determined using purified diets; nevertheless, canned commercial diets formulated primarily with fish should contain more than 60 micrograms K1/kg diet.